Trial Outcomes & Findings for Enfuvirtide/Current Protease Inhibitor Switch to PREZISTA (Darunavir)/Ritonavir + TMC125 in HIV Patients With Enfuvirtide Side Effects. (NCT NCT00460746)
NCT ID: NCT00460746
Last Updated: 2013-07-31
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
10 participants
Primary outcome timeframe
48 weeks
Results posted on
2013-07-31
Participant Flow
Participant milestones
| Measure |
Darunavir(TMC114)/Eravirine(TMC125)
Darunavir/ritonavir (DRV/r) combined with Etravirine (\[ETR\] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
|
|---|---|
|
Overall Study
STARTED
|
10
|
|
Overall Study
COMPLETED
|
8
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Darunavir(TMC114)/Eravirine(TMC125)
Darunavir/ritonavir (DRV/r) combined with Etravirine (\[ETR\] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
|
|---|---|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
Baseline Characteristics
Enfuvirtide/Current Protease Inhibitor Switch to PREZISTA (Darunavir)/Ritonavir + TMC125 in HIV Patients With Enfuvirtide Side Effects.
Baseline characteristics by cohort
| Measure |
Darunavir(TMC114)/Eravirine(TMC125)
n=10 Participants
Darunavir/ritonavir (DRV/r) combined with Etravirine (\[ETR\] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
|
|---|---|
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Age Continuous
|
48 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
6 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
4 participants
n=5 Participants
|
|
Viral Load <50 copies/mL
|
10 participants
n=5 Participants
|
|
CD4 count
|
301 cells/mm^3
n=5 Participants
|
PRIMARY outcome
Timeframe: 48 weeksPopulation: ITT population. One subject (001) who discontinued due to adverse events had a VL \< 50 copies/mL at Week 4. Another subject (013) who was lost to follow-up had VL \<50 copies/mL through Week 36.
Outcome measures
| Measure |
Darunavir(TMC114)/Eravirine(TMC125)
n=10 Participants
Darunavir/ritonavir (DRV/r) combined with Etravirine (\[ETR\] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
|
|---|---|
|
Proportion of Patients Who Maintain Plasma HIV Viral Load Measurements < 400 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure.
Baseline (Day 1)
|
100 percentage of participants
|
|
Proportion of Patients Who Maintain Plasma HIV Viral Load Measurements < 400 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure.
Week 2
|
100 percentage of participants
|
|
Proportion of Patients Who Maintain Plasma HIV Viral Load Measurements < 400 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure.
Week 4
|
100 percentage of participants
|
|
Proportion of Patients Who Maintain Plasma HIV Viral Load Measurements < 400 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure.
Week 8
|
90 percentage of participants
|
|
Proportion of Patients Who Maintain Plasma HIV Viral Load Measurements < 400 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure.
Week 12
|
80 percentage of participants
|
|
Proportion of Patients Who Maintain Plasma HIV Viral Load Measurements < 400 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure.
Week 16
|
90 percentage of participants
|
|
Proportion of Patients Who Maintain Plasma HIV Viral Load Measurements < 400 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure.
Week 24
|
90 percentage of participants
|
|
Proportion of Patients Who Maintain Plasma HIV Viral Load Measurements < 400 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure.
Week 36
|
90 percentage of participants
|
|
Proportion of Patients Who Maintain Plasma HIV Viral Load Measurements < 400 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure.
Week 48
|
80 percentage of participants
|
|
Proportion of Patients Who Maintain Plasma HIV Viral Load Measurements < 400 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure.
Post-Treatment Follow Up
|
90 percentage of participants
|
SECONDARY outcome
Timeframe: 48 weeksPopulation: ITT population. One subject (001) who discontinued due to adverse events had a VL \< 50 copies/mL at Week 4. Another subject (013) who was lost to follow-up had VL \<50 copies/mL through Week 36.
Outcome measures
| Measure |
Darunavir(TMC114)/Eravirine(TMC125)
n=10 Participants
Darunavir/ritonavir (DRV/r) combined with Etravirine (\[ETR\] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
|
|---|---|
|
Proportion of Patients Who Have Viral Load Measurements <50 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure.
Baseline (Day 1)
|
100 percentage of participants
|
|
Proportion of Patients Who Have Viral Load Measurements <50 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure.
Week 2
|
90 percentage of participants
|
|
Proportion of Patients Who Have Viral Load Measurements <50 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure.
Week 4
|
90 percentage of participants
|
|
Proportion of Patients Who Have Viral Load Measurements <50 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure.
Week 8
|
90 percentage of participants
|
|
Proportion of Patients Who Have Viral Load Measurements <50 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure.
Week 12
|
80 percentage of participants
|
|
Proportion of Patients Who Have Viral Load Measurements <50 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure.
Week 16
|
90 percentage of participants
|
|
Proportion of Patients Who Have Viral Load Measurements <50 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure.
Week 24
|
90 percentage of participants
|
|
Proportion of Patients Who Have Viral Load Measurements <50 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure.
Week 36
|
90 percentage of participants
|
|
Proportion of Patients Who Have Viral Load Measurements <50 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure.
Week 48
|
80 percentage of participants
|
|
Proportion of Patients Who Have Viral Load Measurements <50 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure.
Post-Treatment Follow Up
|
90 percentage of participants
|
SECONDARY outcome
Timeframe: Week 48Population: Intent To Treat (ITT), last observation carried forward (LOCF).
Outcome measures
| Measure |
Darunavir(TMC114)/Eravirine(TMC125)
n=10 Participants
Darunavir/ritonavir (DRV/r) combined with Etravirine (\[ETR\] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
|
|---|---|
|
CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline at 4, 8, 12, 16, 24, 36 and 48 Weeks.
Baseline (Day 1)
|
301.0 cells/mm^3
Interval 187.0 to 663.0
|
|
CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline at 4, 8, 12, 16, 24, 36 and 48 Weeks.
Week 4 Change from Baseline
|
-12.0 cells/mm^3
Interval -32.0 to 61.0
|
|
CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline at 4, 8, 12, 16, 24, 36 and 48 Weeks.
Week 8 Change from Baseline
|
-32.0 cells/mm^3
Interval -169.0 to 81.0
|
|
CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline at 4, 8, 12, 16, 24, 36 and 48 Weeks.
Week 12 Change from Baseline
|
-17.0 cells/mm^3
Interval -100.0 to 61.0
|
|
CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline at 4, 8, 12, 16, 24, 36 and 48 Weeks.
Week 16 Change from Baseline
|
-7.0 cells/mm^3
Interval -73.0 to 81.0
|
|
CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline at 4, 8, 12, 16, 24, 36 and 48 Weeks.
Week 24 Change from Baseline
|
19.0 cells/mm^3
Interval -36.0 to 71.0
|
|
CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline at 4, 8, 12, 16, 24, 36 and 48 Weeks.
Week 36 Change from Baseline
|
38.0 cells/mm^3
Interval -59.0 to 117.0
|
|
CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline at 4, 8, 12, 16, 24, 36 and 48 Weeks.
Week 48 Change from Baseline
|
63.5 cells/mm^3
Interval -53.0 to 100.0
|
SECONDARY outcome
Timeframe: Week 48Population: ITT , LOCF.
Outcome measures
| Measure |
Darunavir(TMC114)/Eravirine(TMC125)
n=10 Participants
Darunavir/ritonavir (DRV/r) combined with Etravirine (\[ETR\] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
|
|---|---|
|
CD4+ Cell Count (x 10^6 Cell/L): Baseline and Mean Changes From Baseline at 4, 8, 12, 16, 24,36 and 48 Weeks.
Baseline (Day 1)
|
338.3 cells/mm^3
Standard Deviation 135.91
|
|
CD4+ Cell Count (x 10^6 Cell/L): Baseline and Mean Changes From Baseline at 4, 8, 12, 16, 24,36 and 48 Weeks.
Week 4 Change from Baseline
|
2.3 cells/mm^3
Standard Deviation 31.22
|
|
CD4+ Cell Count (x 10^6 Cell/L): Baseline and Mean Changes From Baseline at 4, 8, 12, 16, 24,36 and 48 Weeks.
Week 8 Change from Baseline
|
-25.0 cells/mm^3
Standard Deviation 72.04
|
|
CD4+ Cell Count (x 10^6 Cell/L): Baseline and Mean Changes From Baseline at 4, 8, 12, 16, 24,36 and 48 Weeks.
Week 12 Change from Baseline
|
-18.9 cells/mm^3
Standard Deviation 44.25
|
|
CD4+ Cell Count (x 10^6 Cell/L): Baseline and Mean Changes From Baseline at 4, 8, 12, 16, 24,36 and 48 Weeks.
Week 16 Change from Baseline
|
0.5 cells/mm^3
Standard Deviation 53.58
|
|
CD4+ Cell Count (x 10^6 Cell/L): Baseline and Mean Changes From Baseline at 4, 8, 12, 16, 24,36 and 48 Weeks.
Week 24 Change from Baseline
|
24.5 cells/mm^3
Standard Deviation 34.00
|
|
CD4+ Cell Count (x 10^6 Cell/L): Baseline and Mean Changes From Baseline at 4, 8, 12, 16, 24,36 and 48 Weeks.
Week 36 Change from Baseline
|
22.7 cells/mm^3
Standard Deviation 58.84
|
|
CD4+ Cell Count (x 10^6 Cell/L): Baseline and Mean Changes From Baseline at 4, 8, 12, 16, 24,36 and 48 Weeks.
Week 48 Change from Baseline
|
47.3 cells/mm^3
Standard Deviation 48.03
|
SECONDARY outcome
Timeframe: Week 48Population: ITT , LOCF.
Outcome measures
| Measure |
Darunavir(TMC114)/Eravirine(TMC125)
n=10 Participants
Darunavir/ritonavir (DRV/r) combined with Etravirine (\[ETR\] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
|
|---|---|
|
Median Change From Baseline in Triglycerides at Week 48.
Baseline (Day 1)
|
229.0 mg/dL
Interval 121.0 to 402.0
|
|
Median Change From Baseline in Triglycerides at Week 48.
Week 48 Change from Baseline
|
-24.5 mg/dL
Interval -227.0 to 78.0
|
SECONDARY outcome
Timeframe: Week 48Population: ITT , LOCF.
Outcome measures
| Measure |
Darunavir(TMC114)/Eravirine(TMC125)
n=10 Participants
Darunavir/ritonavir (DRV/r) combined with Etravirine (\[ETR\] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
|
|---|---|
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Median Change From Baseline in Total Cholesterol at Week 48.
Baseline (Day 1)
|
189.0 mg/dL
Interval 159.0 to 244.0
|
|
Median Change From Baseline in Total Cholesterol at Week 48.
Week 48 Change from Baseline
|
-27.5 mg/dL
Interval -44.0 to 27.0
|
SECONDARY outcome
Timeframe: Week 48Population: ITT , LOCF.
Outcome measures
| Measure |
Darunavir(TMC114)/Eravirine(TMC125)
n=10 Participants
Darunavir/ritonavir (DRV/r) combined with Etravirine (\[ETR\] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
|
|---|---|
|
Median Change From Baseline in LDL Cholesterol at Week 48.
Baseline (Day 1)
|
100.0 mg/dL
Interval 63.0 to 149.0
|
|
Median Change From Baseline in LDL Cholesterol at Week 48.
Week 48 Change from Baseline
|
-9.0 mg/dL
Interval -30.0 to 17.0
|
SECONDARY outcome
Timeframe: Week 48Population: ITT , LOCF.
Outcome measures
| Measure |
Darunavir(TMC114)/Eravirine(TMC125)
n=10 Participants
Darunavir/ritonavir (DRV/r) combined with Etravirine (\[ETR\] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
|
|---|---|
|
Median Change From Baseline in HDL Cholesterol.
Baseline (Day 1)
|
47.5 mg/dL
Interval 25.0 to 54.0
|
|
Median Change From Baseline in HDL Cholesterol.
Week 48 Change from Baseline
|
-2.5 mg/dL
Interval -15.0 to 10.0
|
SECONDARY outcome
Timeframe: Week 48Population: ITT , LOCF.
Outcome measures
| Measure |
Darunavir(TMC114)/Eravirine(TMC125)
n=10 Participants
Darunavir/ritonavir (DRV/r) combined with Etravirine (\[ETR\] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
|
|---|---|
|
Median Change From Baseline in Total Cholesterol (TC) / High Denisty Lipoprotein (HDL) Ratio at Week 48.
Baseline (Day 1)
|
4.7 ratio of TC and HDL
Interval 2.94 to 6.4
|
|
Median Change From Baseline in Total Cholesterol (TC) / High Denisty Lipoprotein (HDL) Ratio at Week 48.
Week 48 Change from Baseline
|
-0.3 ratio of TC and HDL
Interval -0.82 to 1.2
|
SECONDARY outcome
Timeframe: Week 48Population: ITT , LOCF.
Outcome measures
| Measure |
Darunavir(TMC114)/Eravirine(TMC125)
n=10 Participants
Darunavir/ritonavir (DRV/r) combined with Etravirine (\[ETR\] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
|
|---|---|
|
Median Change From Baseline in Glucose at Week 48.
Baseline (Day 1)
|
92.5 mg/dL
Interval 74.0 to 105.0
|
|
Median Change From Baseline in Glucose at Week 48.
Week 48 Change from Baseline
|
1.0 mg/dL
Interval -21.0 to 12.0
|
Adverse Events
Darunavir(TMC114)/Eravirine(TMC125)
Serious events: 1 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Darunavir(TMC114)/Eravirine(TMC125)
n=10 participants at risk
Darunavir/ritonavir (DRV/r) combined with Etravirine (\[ETR\] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
|
|---|---|
|
Hepatobiliary disorders
Cholecystitis acute
|
10.0%
1/10 • Number of events 1
|
Other adverse events
| Measure |
Darunavir(TMC114)/Eravirine(TMC125)
n=10 participants at risk
Darunavir/ritonavir (DRV/r) combined with Etravirine (\[ETR\] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
|
|---|---|
|
General disorders
Abdominal pain upper
|
10.0%
1/10 • Number of events 1
|
|
Nervous system disorders
Amnesia
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
10.0%
1/10 • Number of events 1
|
|
Metabolism and nutrition disorders
Decreased appetite
|
10.0%
1/10 • Number of events 1
|
|
Psychiatric disorders
Depression
|
20.0%
2/10 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhea
|
30.0%
3/10 • Number of events 3
|
|
Nervous system disorders
Disturbance in attention
|
10.0%
1/10 • Number of events 1
|
|
Infections and infestations
Diverticulitis
|
10.0%
1/10 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Dry mouth
|
10.0%
1/10 • Number of events 1
|
|
General disorders
Fatigue
|
40.0%
4/10 • Number of events 4
|
|
Nervous system disorders
Headache
|
30.0%
3/10 • Number of events 3
|
|
Vascular disorders
Heart rate increase
|
10.0%
1/10 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
10.0%
1/10 • Number of events 1
|
|
Vascular disorders
Hypertension
|
20.0%
2/10 • Number of events 2
|
|
Psychiatric disorders
Insomnia
|
20.0%
2/10 • Number of events 2
|
|
Gastrointestinal disorders
Nausea
|
10.0%
1/10 • Number of events 1
|
|
General disorders
Pain
|
10.0%
1/10 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash
|
30.0%
3/10 • Number of events 3
|
|
Nervous system disorders
Somnolence
|
10.0%
1/10 • Number of events 1
|
Additional Information
Vice President, Tibotec Therapeutics Clinical Affairs
Tibotec Therapeutics Clinical Affairs, Division of Centocor Ortho Biotech Services, LLC
Phone: 877-732-2488
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee If TTCA does not publish within 12 months after study conclusion or after TTCA confirms there will be no multicenter publication, Institution may publish their results from their site individually, provided TTCA has 60 day review for confidentiality and additional 60 day delay for patent application.
- Publication restrictions are in place
Restriction type: OTHER